The long-term objective of this research is to understand the molecular basis of ion selectivity and gating regulation in K+ channels. Potassium channels produce electrical signals in nerve cells, control the pace of the heart, and allow hormones to be secreted into the bloodstream. The first specific aim addresses the mechanism by which K+ channels discriminate between K+ and Na+ ions, a property essential to cell biology. Electrophysiology and x-ray crystallography techniques will be used to characterize ion coordination in the pore. The second specific aim seeks to understand the role of voltage dependent K+ channel Beta subunits in cell biology. These subunits attach to K+ channels at the cell membrane's inner surface and they have enzymatic potential. They are ubiquitous in the brain and have been implicated in the control of neural excitability and in sensing oxygen levels. Electrophysiology and x-ray techniques will be used to study Beta subunit function. The third specific aim focuses on a structural component of the HERG K+ channel that controls its gating. The HERG K+ channel governs electrical activity of the heart; its malfunction is a cause of sudden death by cardiac arrhythmia.